The current investigation examines the significance of estrogen in central cardiovascular regulatory nuclei in modulating autonomic tone and baroreceptor reflex function. Experiments were done in anaesthetized male Sprague-Dawley rats. Changes in autonomic tone were assessed by monitoring vagal and renal efferent nerve activities before and following bilateral injection of estrogen into select central autonomic nuclei. In the first study, selective blockade of neurotransmission through the central nucleus of the amygdala (CNA), lateral hypothalamic area (LHA) and ventral posteromedial thalamic nucleus (VPM) using the local anaesthetic lidocaine was done to determine which nuclei were involved in mediating the autonomic changes observed following bilateral injections of estrogen into the insular cortex (IC). In the second study, the role of the parabrachial nucleus (PBN) in mediating the autonomic changes observed following bilateral estrogen injections into the CNA, LHA, VPM and IC was determined by blocking neurotransmission through the PBN using lidocaine.Injections of estrogen into the IC produced a significant increase in renal sympathetic nerve activity (RSNA; from 10+/-2 to 24+/-4 microV/sec; p0.05). Injection of estrogen into the CNA resulted in a significant decrease in RSNA (48+/-5%; p<0.05) whereas estrogen injection into the LHA resulted in a significant increase (28+/-4%; p<0.05) in RSNA. Pre-injection of lidocaine into the PBN resulted in complete blockade of the autonomic changes observed following estrogen injection into the CNA but did not affect the changes observed following estrogen injection into the LHA. These results suggest that estrogen acting in forebrain and midbrain cardiovascular nuclei activated efferent pathways which synapse in the LHA, CNA and/or PBN prior to projecting to autonomic preganglionic nuclei to affect autonomic tone. These nuclei may therefore provide an added level of processing and/or integration of the autonomic response(s) following activation by local or systemic estrogen.